Tuberculosis

Question 1

Isoniazid: Dosage form? Dose? Metabolism? Toxicities?

Answer 1

Dosage form: Oral, IM, IV

Dose: 300 mg QD // 10-20 mg/kg for kids

Cleared liver more than kidney

Toxicities: Hepatotoxicity, peripheral neuropathy

Question 2

Rifampin: Dosage form? Dose? Metabolism? Toxicities?

Answer 2

Dosage form: Oral, IV

Dose: 600 mg QD // 10-20 mg/kg for kids

Cleared liver more than kidney

Toxicities: hepatotoxicity, flu-like syndrome

Question 3

Rifapentine: Dosage form? Dose? Metabolism? Toxicities?

Answer 3

Dosage forms: Oral only

Dose: 600 mg QD // moving to 1200 mg QD

Cleared by liver more than kidney

Toxicities: hepatotoxicity, flu-like syndrome

Question 4

Rifabutin: Dosage form? Dose? Metabolism? Toxicities?

Answer 4

Use for HIV+ patientsA

Dosage forms: oral

Dose: 300 mg (150-450 mg) QD

Metabolism: Liver more than kidneys

Toxicities: Neutropenia, thrombocytopenia, uveitis

Question 5

Which rifamycin is best for someone on a lot of drugs?

Answer 5

Rifabutin - least amount of CYP3A4 induction

Question 6

Pyrazinamide: Dosage form? Dose? Metabolism? Toxicities?

Answer 6

Dosage form: Oral

Dose: 35-40 mg/kg QD (adults and kids)

Cleared by liver, then metabolites are cleared by kidneys

Toxicities: Hepatotoxicity, elevated uric acid

Question 7

How can you tell a patient is non-adherent on PZA?

Answer 7

If their uric acid is normal, they’re not being adherent. PZA causes uric acid levels to rise.

Question 8

Ethambutol: Dosage form? Dose? Metabolism? Toxicities?

Answer 8

4th drug in case of resistance

Dosage: oral

Dose: 15-25 mg/kg QD (adults and kids)

Cleared: KIDNEYSSSS over liver

Toxicity: Ocular toxicity, rashes

Question 9

What drug should be adjusted renally?

Answer 9

Ethambutol, Streptomycin, levofloxacin, cycloserine

Question 10

Streptomycin: Dosage form? Dose? Metabolism? Toxicities?

Answer 10

Role: Fourth drug in case of resistance

Dosage: IM, IV

Dose: 12-15 mg/kg QD (adults and kids)

Cleared: Kidneys

Toxicity: Ototoxicity, nephrotoxicity, cation loss

Question 11

Amikacin, Kanamycin, Capreomycin - role?

Answer 11

Drug resistant TB

Question 12

Levofloxacin: Dosage? Dose? Metabolism? Toxicities?

Answer 12

Oral, IV

750 - 1000 mg QD

Kidneys

Toxicities: Dizziness, GI, tendonitis

Question 13

Moxifloxacin: Dosage? Dose? Metabolism? Toxicities?

Answer 13

Oral, IV

400 mg QD

Kidneys and liver

Dizziness, GI, tendonitis

Question 14

Ethionamide: Dosage form? Dose? Metabolism? Toxicities?

Answer 14

Drug resistant TB

Oral

250-500 mg BID
10-20 mg/kg divided BID for kids

Cleared by liver

Toxicities: GI upset, hypothyroidism

Question 15

p-Aminosalicylic Acid: Dosage form? Dose? Metabolism? Toxicities?

Answer 15

Drug resistant TB

Role: Drug resistant TB

Dosage: Oral

Dose: 4000 mg BID-TID // 150 mg/kg divided BID-TID

Cleared liver over kidneys

Toxicities: GI upset, hypothyroidism

Question 16

Cycloserine: Dosage form? Dose? Metabolism? Toxicities?

Answer 16

Drug resistant TB

Oral

250-500 mg BID // 10-20 mg/kg divided BID for kids

Cleared by kidneys

Toxicities: lack of concentration, altered behavior

Question 17

First line treatment for latent TB infection?

Answer 17

INH 300 mg QD for 9 months
or
900 mg (15 mg/kg) twice weekly DPOT

Question 18

Second line treatment for latent TB infection?

Answer 18

Rifapentine 900 mg PLUS INH 900 mg (once weekly for 12 doses)

Question 19

Third line treatment for latent TB infection?

Answer 19

Rifampin 600 mg QD for 4 months

Could also sub Rifabutin 300 mg (less drug interactions, good for HIV pts)

Question 20

Fourth line treatment for latent TB (INH & RIF resistant suspected)?

Answer 20

Ethambutol 15 mg/kg QD plus Levo 750 mg QD for 6-12 months

or

PZA 25 mg/kg QD + Levo 750 mg QD for 6-12 months (not well tolerated)

Question 21

How to treat active disease?

Answer 21

For drug-susceptible TB (60 kg male)
For first 8 weeks:
Isoniazid 300 mg 5x weekly (5 mg/kg)
Rifampin 600 mg 5x weekly (10 mg/kg)
Pyrazinamide 1500 mg 5 x weekly (25 mg/kg)
plus
Ethambutol 1200 mg 5 x weekly (20 mg/kg) until TB drug-susceptibility documented

then Isoniazid 300 mg 5 x weekly (5 mg/kg) and Rifampin 600 mg 5 x weekly (10 mg/kg) for at least 4 more months (6 months total)

Drop the PZA and Ethambutol

Question 22

Duration of treatment for active TB infection?

Answer 22

Uncomplicated: 6 months total at least

HIV: Extend therapy to 9 months if they have a positive culture at 2 months or delayed clinical response to therapy

Meningitis: 9-12 months

Bone TB: 6-9 months

Question 23

How to treat MDR TB?

Answer 23

No standard or twice weekly regimens, treat for 18 to 30 months, DPOT essential

Question 24

What TB drugs are CYP3A4 inducers?

Answer 24

Rifampin, rifapentine, rifabutine

Question 25

What TB drugs are CYP3A4 inhibitors?

Answer 25

Amprenavir, ritonavir, saquinavir, cobicistat

Question 26

What effect do rifamycins have on HAART?

Answer 26

PI’s - rifamycins decrease levels

Darunavir/ritonavir
Fosamprenavir/ritonavir
Lopinavir/ritonavir
Atazanavir/ritonavir

All decreased under rifampin, only first 2 are decreased by rifabutin

Rifamycins decrease Etravirine, rilpivirine, efavirenz (not rifabutin)

Question 27

What effect does HAART have on rifamycins?

Answer 27

PI’s all increase rifabutin, no change on rifampin

Rifabutin is preferred in HIV!